10-76246379-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):c.517-78022A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,004 control chromosomes in the GnomAD database, including 22,430 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22430 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.517-78022A>G		intron_variant		ENST00000611255.5
LRMDA	NM_032024.5	c.433-78022A>G		intron_variant
LRMDA	NR_131178.2	n.871-78022A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-78022A>G		intron_variant		5	NM_001305581.2	P1
LRMDA	ENST00000372499.5	c.433-78022A>G		intron_variant		1
LRMDA	ENST00000593699.5	n.871-78022A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82218 AN: 151886 Hom.: 22415 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82255 AN: 152004 Hom.: 22430 Cov.: 32 AF XY: 0.542 AC XY: 40252 AN XY: 74290

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.573

Alfa AF: 0.543 Hom.: 3802

Bravo AF: 0.546

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.6
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1247487; hg19: chr10-78006137;